维生素D受体基因与骨量的关系

近年来对维生素D受体(VDR)基因和骨量关系的研究颇有争议。有许多研究认为维生素D受体基因多态性与骨量有关联。但还有一部分研究未能证实VDR基因多态性与骨量的关联。本文就VDR基因与钙吸收、骨量、药物治疗的关系和VDR基因的协同作用以及与其它基因、环境因素的交互作用对骨量影响的研究进展进行了综述。     

维生素D受体和雌激素受体的基因与骨质疏松

骨质疏松症是以低骨量和骨组织微结构退化为特征的全身性疾病,与众多因素有关,而遗传是其中的重要决定因素。在目前研究的若干侯选基因中,维生素D受体基因与雌激素受体基因最受瞩目。该文就维生素D受体基因,雌激素受体基因与骨质疏松的关系及这两个基因之间的协同作用进行综述,从而阐明维生素D受体基因与雌激素受体基因在骨质疏松症发病机制中的作用。     

维生素D受体基因(VDR)多态性与儿童铅中毒易感性的研究

目的:观察维生素D受体(VDR)基因rs731236、rs1544410及rs7975232在深圳市儿童血铅≥60μg/L样本组和低铅对照组之间的分布,揭示VDR基因多态性与儿童铅中毒易感的相关性。方法:在6个月～6岁儿童中筛选出75例样本组(血铅≥60μg/L均值(X=82.24μg/L)和80例对照组(血铅均值X=19.90μg/L)的样本,用PCR方法对VDR基因rs731236、rs1544410及rs7975232进行扩增,采用基质辅助激光解吸电离飞行时间质谱分析法(MALDI-TOF-MS)鉴定其基因型,比较各基因型在两组间的分布,寻找其与儿童血铅值的关系。结果:VDR基因rs731236中的基因型TT在样本组与对照组的分布频率差异有统计学意义(P<0.05),rs1544410中的GG在样本组与对照组的分布频率差异有统计学意义(P<0.01),rs7975232多态性在样本组与对照组的分布频率差异无统计学意义(P>0.05)。结论:VDR基因rs731236中的TT和rs1544410中的GG基因型可能增加儿童铅中毒的危险性;作为铅中毒的易感基因筛查值得进一步探讨。     

Short-term regulation of the renal vitamin D receptor in rats by 1,25-dihydroxycholecalciferol is calcium insensitive.

Acute regulation of the vitamin D receptor in kidney by 1,25-dihydroxycholecalciferol and dietary calcium was investigated using vitamin D-deficient rats. 1,25-Dihydroxycholecalciferol administered to normocalcemic, vitamin D-deficient rats increased the renal receptor level, whereas serum calcium and phosphorus concentrations remained nearly constant. In hypocalcemic, vitamin D-deficient rats, 1,25-dihydroxycholecalciferol caused a sharp response at 4 h, which remained elevated for the remaining 20 h. Serum calcium rose gradually over 24 h, whereas serum phosphorus remained fairly constant. When hypocalcemic, vitamin D-deficient rats were fed a high calcium diet following 14 h without food, the serum calcium concentration increased and serum phosphorus concentration decreased, whereas renal receptor levels were unchanged. These data indicate that 1,25-dihydroxycholecalciferol rapidly regulates the renal vitamin D receptor, independent of serum calcium and phosphorus, but requires an adequate serum calcium concentration to sustain a prolonged effect.     

Novel Intracellular Proteins Associated with Cellular Vitamin D Action

Work with vitamin D–resistant New World primates has revealed novel cellular proteins involved in vitamin D action. An "intracellular vitamin D–binding protein" functions to bind vitamin D metabolites in the cell and enhances vitamin D action. By contrast, a "vitamin D response element–binding protein" inhibits vitamin D receptor binding to the DNA and is responsible for vitamin D resistance in New World primates.     

维生素D受体与阿尔茨海默病关系的研究

低水平维生素D与认知能力的下降密切相关,针对维生素D受体作用机制及其与阿尔茨海默病之间的关系进行深入探讨,以期探索出阿尔茨海默病的治疗方法。     

Vitamin D and vitamin D analogs as cancer chemopreventive agents

Epidemiologic studies have associated vitamin D, attained through nutrition and sun exposure, with reduced cancer risk. Although dose-limiting hypercalcemia has limited the use of natural vitamin D in cancer prevention, several promising new synthetic vitamin D analogs (deltanoids) are under development. Examples are KH-1060, EB-1089, 1alpha-hydroxyvitamin D5, vitamin D2, and QW-1624F2-2. Clinical targets for deltanoids include colon, prostate, and breast. Studies to elucidate the molecular mechanisms underlying the observed efficacy of deltanoids are ongoing. The vitamin D receptor, a steroid/thyroid receptor superfamily member, appears to control most deltanoid effects on proliferation, apoptosis, differentiation, and angiogenesis.     

川崎病儿童血清维生素D水平及其受体Fok Ⅰ基因多态性研究

目的分析潍坊地区川崎病儿童血清25-羟基维生素D3[25-(OH)D3]水平及其受体Fok Ⅰ基因多态性,探讨维生素D水平与川崎病冠脉损伤发生的相关性。方法采用病例-对照的研究方法,以98例川崎病患儿为病例组,根据有无冠状动脉损伤(CAL)分为冠脉损伤组(CAL组) 24例和非冠脉损伤组(NCAL组) 74例,选择同期80例健康儿童为对照组,通过酶联免疫法检测各组儿童血清25-(OH)D3水平,采用PCR聚合酶链反应和基因测序法对维生素D受体(VDR) Fok Ⅰ位点基因多态性进行检测,并对3组儿童的基因型和等位基因频率进行比较。结果 CAL组和NCAL组患儿25-(OH)D3水平低于对照组儿童,以CAL组最低,3组差异均有统计学意义(P<0. 05)。儿童VDR基因Fok Ⅰ位点不同基因型在川崎病组和对照组中的分布差异有统计学意义(P<0. 05),在CAL组和NCAL组间差异无统计学意义(P>0. 05)。结论维生素D缺乏可能是川崎病发病的危险因素之一,VDR Fok Ⅰ多态性与川崎病发病有一定相关性。     

Adolescent vitamin A intake alters susceptibility to mammary carcinogenesis in the Sprague-Dawley rat

We tested the hypothesis that adolescent dietary vitamin A intake impacts mammary gland development and subsequent sensitivity to carcinogenesis. Sprague-Dawley rats were fed a purified diet that was vitamin A deficient, adequate (2.2 mg retinyl palmitate/kg diet), or supranutritional (16 mg retinyl palmitate/kg diet) from 21 to 63 days of age, the period of adolescent mammary gland development. At 73 days of age, rats were given 1-methyl-1-nitrosourea (25 mg/kg body wt i.p.) and monitored for mammary tumors. Tumors appeared earlier and more frequently in rats fed vitamin A-deficient or -supplemented diets. Vitamin A deficiency during adolescence was associated with alveolar mammary gland development and precocious milk protein expression, while supplementation was associated with ductal gland development and suppression of milk protein expression. Differences in circulating estradiol and mammary gland estrogen receptor-alpha, and estrogen-responsive progesterone receptor mRNA were not observed, suggesting that the effects of vitamin A on mammary gland development and carcinogenesis are estrogen independent. Mammary expression of another hormone receptor that regulates milk protein expression, the glucocorticoid receptor, was also unaffected. These results demonstrate that vitamin A intake during adolescence alters mammary gland differentiation and indicate that a narrow range of vitamin A intake during adolescence protects against carcinogenesis.     

Vitamin D and respiratory infection in adults

Vitamin D insufficiency is a global issue that has significant implications for health. The classical role of vitamin D in bone mineralisation is well known; vitamin D deficiency leads to rickets, osteomalacia or osteoporosis. The role of vitamin D in an immune system is less known. Vitamin D is not an actual vitamin but a secosteroid hormone produced in the skin from 7-dehydrocholesterol after exposure to sunlight UVB radiation. Nutrition and supplements are main sources of vitamin D in wintertime in northern countries as sunlight exposure is inadequate for the production. For activation vitamin D needs to be hydroxylated in liver to form 25-hydroxyvitamin D and in kidney to 1,25-dihydroxyvitamin D, the most active hormone in Ca absorption in the gut. For determination of vitamin D status serum 25-hydroxyvitamin D level, the major circulating form of the hormone is to be measured. Vitamin D regulates gene expression through binding with vitamin D receptors, which dimerises with retinoid X receptor. This complex binds to vitamin D-responsive elements inside the promoter regions of vitamin D-responsive genes. Vitamin D has a key role in innate immunity activation; the production of antimicrobial peptides (cathelicidin and defensins) following Toll-like receptor stimulation by pathogen lipopeptides is dependent on sufficient level of 25-hydroxyvitamin D. Clinically, there is evidence of the association of vitamin D insufficiency and respiratory tract infections. There is also some evidence of the prevention of infections by vitamin D supplementation. Randomised controlled trials are warranted to explore this preventive effect.     

维生素D受体在肠道肿瘤生长中与β-catenin通路之间的关系

目的探讨维生素D受体（VDR）对肠道肿瘤生长的影响以及与β-catenin信号通路之间的关系。方法体外培养的人类结肠癌SW480细胞株经维生素D处理4h,免疫沉淀法检测VDR和t3-catenin蛋白的交互作用,24h后用Westernblot检测细胞E．cadherin蛋白的表达。体内实验比较APCmin／＋VDR-／-与APCmin／＋小鼠,免疫组化法检测两型小鼠肠道肿瘤VDR、β-catenin和Brdu蛋白的表达,Westernblot检测肿瘤和肿瘤旁组织β-catenin蛋白的表达。结果维生素D处理SW480细胞后,VDR和β-catenin蛋白相互结合,随后E-cadherin蛋白表达增高（对照组灰度值145．57±4．21,实验组109．35±3．56,t=32．63,P〈0．05）。缺失VDR的APCmin／＋VDR-／-小鼠肠道肿瘤中β-catenin蛋白表达免疫组化（灰度值140．51±2．57）及Westemblot（灰度值166．47±2．36）检测均高于APCmin／＋肿瘤（分别为145．41±3．62、182．35±3．24,t=2．65,4．36,P〈0．05）。结论维生素D抑制肠道肿瘤增殖的作用可能通过VDR影响β-catenin信号通路来完成。     

The role of estrogen receptor, vitamin D receptor and calcium receptor genotypes in the pathogenesis of colorectal cancer

In this study, the Xbal polymorphisms of the estrogen-, the Bsml polymorphism of the vitamin D- as well as the A986S polymorphism of the calcium-sensing receptor genes were investigated in 56 patients with colorectal cancer. The expression of erbB-2, epidermal growth factor receptor, ras, p53 and their relationship to estrogen-, vitamin D- and calcium-sensing receptor genotypes were also studied. In subjects exhibiting XX genotype of the estrogen receptor gene or bb genotype of the vitamin D receptor gene, erbB-2 expression was significantly lower compared to those with xx, Xx or BB, Bb (6/56 and 11/56 vs. 31/56 and 26/56; p = 0.0043 and 0.041). The presence of the XX alleles of estrogen receptor gene significantly correlated with the overexpression of the epidermal growth factor receptor expression in tumors, whereas in xx and Xx genotypes, significantly higher expression was seen (7/56 vs. 30/56; p = 0.049). Analyzing the combinations of the two gene allelic variants, we have found XXbb genotype to be associated with a significantly lower erbB-2 expression, compared to other combinations (Xxbb, XxBb, XXBb) (2/7 vs. 7/7, 4/5, 4/5; p = 0.0011). Patients with AA calcium-sensing receptor genotype were in higher UICC stages at the time of discovery of their disease than those with AS genotype. The AA allelic variant of the calcium-sensing gene was more frequent among patients with colorectal cancer compared to controls (36/56 vs. 36/112; p = 0.0004). Our observations raise the possibility that estrogen-, and vitamin D receptor gene polymorphisms accompanied with variable oncogene expression might influence the pathogenic processes resulting in the development of colorectal cancer. The A986S polymorphism of calcium-sensing receptor might also be a prognostic marker of the disease.     

维生素D3类似物治疗白癜风分子生物学机制及临床应用现状

维生素 D3 活性代谢产物 1,25（OH）2D3 及其类似物通过维生素 D 受体 （VDR） 发挥对表皮黑素单位的保护作用.近年来研究表明,维生素 D3 类似物单独或联合应用紫外线或皮质类固醇激素可以提高白癜风皮损的复色.因此,进一步了解维生素 D3 类似物在白癜风复色中的作用机制,研制新的、高效的维生素 D3 类似物,对白癜风的治疗具有重要意义.     

Understanding the role of vitamin A and its precursors in the immune system

Vitamin A is the first defined vitamin and is also known as an anti-inflammatory micronutrient. Although the primary biological function is preservation of epithelial tissue integrity, vision and growth, vitamin A also plays a role in immune system regulation. It is known that susceptibility to infections increases in developing countries due to vitamin A deficiency. Therefore, the purpose of this review is to evaluate the role of vitamin A on the immune system in line with current studies. In this review, we focused on the immunobiological effects of vitamin A and its precursors. Vitamin A refers to retinoids and carotenoids, but both function in the body through the most active form, all trans retinoic acid. All trans retinoic acid has the highest affinity of nuclear retinoic acid receptor. Reports from in-vivo and in-vitro studies shown that the formation of retinoic acid/retinoic acid receptor complex is important in the generation of innate and adaptive immune cell response. In addition to immune cell response, vitamin A also plays an important role in mucus secretion, morphological formation and functional maturation of epithelial cells. In this way, vitamin A appears to contribute to immune development by regulating immune cell response and providing mechanistic defense. Vitamin A has received particular attention in recent years as the vitamin have been shown to have a crucial effect on the immune response. Although more randomized controlled studies are needed, data from observational human studies have shown that vitamin A is associated with infectious, inflammatory, allergic diseases and cancers.     

Vitamin D status and the metabolic syndrome

The identification of vitamin D receptor expression in different tissues suggests a widespread role for vitamin D action beyond its classical function in bone and mineral metabolism. Recently, the importance of vitamin D status as a risk factor in the development of metabolic syndrome has been the focus of several studies.